The principle objective of the proposed study is to gain insight into the mechanism of tumorigenesis in the Lucke tumor-Herpes virus system. By utilizing our ability to induce tumors in developing frog embryos, we will approach this basic problem on several levels: 1) through the study of early cellular changes indicative of the transformation to neoplasia in the developing kidney cells; 2) through careful examination of the chromosomes of these young tumors and comparison with the chromosomes of normal cells; 3) through a study of the susceptibility of cells to infection and transformation at various stages of development (can vertical transmission and/or the insertion site of an oncogenic agent be localized on the chromosome level in the Lucke tumor system? When is the genetic information which later directs the cell to become neoplastic incorporated into the cell? Are differentiating cells more susceptible to the activation or incorporation of viral DNA than stem cells or already differentiated cells?); and finally, 4) through a study of the effects of various temperatures on the process of neoplastic transformation in these developing poikilotherms. Because of certain unique aspects of early amphibian development (external fertilization, large size of eggs, large and few chromosomes (n equals 13), ability to produce great numbers of offspring in vitro, etc.), these animals have been used extensively in studies of early vertebrate development. These same attributes render the frog system uniquely suited for the application of embryological approaches to the study of neoplasia, as outlined in the proposed study. Because of these unique features, the frog kidney tumor system has promise of yielding valuable information about the mechanism of tumorigenesis-information which should provide insight into some of the provocative problems encountered in mammalian tumor-virus systems, especially in humans.